Synthesis of peptide inhibitors of renin and kallikrein containing the novel amino acid residues found in the natural peptide antibiotics, pepstatin and leupeptin, is proposed. These synthetic peptides will also have amino acid sequences corresponding to the sequences of the physiological substrates for renin and kallikrein. The combination of the key amino acid residue of the potent natural inhibitors and the physiological amino acid sequence is expected to provide peptides that are effective and specific inhibitors of renin and kallikrein. Since these enzymes are involved in the production of angiotensin II (vaso-constriction) and kinins (vaso-dilation) selective inhibitors of renin and kallikrein, respectively, should allow some control of blood pressure. We will evaluate the biological effects of the synthetic peptides in vitro using radioimmunoassays and appropriate esterase or protease assays. This will allow a rapid determination of the effectiveness of inhibitor's synthesized and of the value of changes made in inhibitor structure in attempts to enhance the selectivity or effectiveness of the inhibitors.